In Vivo Wound-Healing and Molecular Docking Studies Support the Traditional Use of Arisarum Vulgare Aqueous Extract

Abstract

In Algerian traditional medicine, Arisarum vulgare O. Targ. Tozz. (Araceae), locally known as "Elbgouga," is widely used to treat eczema, wounds, and burns. The aim of this study was to investigate, for the first time and by using in vivo and in silico molecular docking techniques, the possible effects of A. vulgare ultrasound-assisted aqueous extract (AVAE) on wound healing. The phytochemical profile was elucidated by LC-ESI-MS/MS analysis. Wistar albino rats were used to evaluate the AVAE ointment's acute cutaneous toxicity and wound-healing potential (1%, 2%, and 5% AVAEO). Through in silico investigations, TNF-alpha, IL-1 beta, MMP-9, TGF-beta, VEGF, and EGFR were examined as possible therapeutic targets. Twenty-seven phytochemicals, belonging mainly to the flavonoids and phenolic acids' class, were identified and semi-quantified. The 5% AVAEO-treated group showed a significantly greater (p < 0.001) wound contraction (8-20 days) with respect to untreated and petroleum jelly groups, whereas no statistically significant difference was observed with respect to the Madecassol-treated group. On the contrary, the two lower doses (1% and 2% AVAEO) showed no statistically significant effects. Docking studies showed that A. vulgare bioactive compounds may have therapeutic effects on wound healing by targeting with high affinity TNF alpha, IL-1 beta, MMP-9, TGF-beta R1, VEGF, and EGFR, counteracting inflammation, angiogenesis, and oxidative unbalance, and promoting wound repair. This study demonstrated that AVAE possesses in vivo wound healing properties and no dermal toxicity, shedding light also on the potential therapeutic targets involved.